This program entitled "Host Factors in Fungal Asthma and Fibrosis" has its goal to translate our basic knowledge in antigen recognition, mechanisms of allergy and tolerance, and high throughput genomics and proteomics to 1) improve our understanding of allergjc and fibrotic lung diseases and 2) use this knowledge to design interventions to prevent or ameliorate these pathogenic processes. Towards this end, this SCCOR application proposes two closely linked clinical and basic science projects. One clinical and basic science project will investigate the role of beta-glucan and the beta-glucan receptor Dectin-1 in the development of allergy or tolerance to the ubiquitous fungus Aspergillus fumigatus. These studies will be conducted in the context of a cohort of patients with Cystic Fibrosis that have defined Aspergillus colonization with and without Allergic Bronchopulmonary Aspergillosis (ABPA) and a basic science project that uses a novel rodent model of immune tolerance or allergy to define the role of the local pulmonary immune system and surfactant proteins in the development of allergy versus tolerance. Another clinical and basic science project will be focused on pulmonary fibrosis. The clinical project will use gene expression and protein expression profiling to better define subgroups of patients with idiopathic pulmonary fibrosis (IPF) as well as further define abnormalities in adaptive T -cell biology that occurs in these patients. A closely linked basic project will investigate the role of KGF and the ligands for CXCR3 (CXCL9, CXCL10, and CXCL11) in regulating the fibrotic response to bleomycin lung injury in rodents. The overall theme of this SCCOR is to define molecular pathways that regulate adaptive immunity to antigens and to improve our understanding of interactions between immune cells and parenchymal cells in the development of fibrosis or in the setting of allergy (or tolerance). These themes are in concert with the goals of the RFA to: characterize innate and adaptive immune responses, develop genomic and proteomic signatures of pulmonary pathways and conduct studies in humans that have direct diagnostic and potentially therapeutic application. The long-term objective of the SCCOR is to use the knowledge of the molecular pathways to improve diagnosis and treatment of patients suffering form chronic lung diseases particularly allergic and fibrotic lung diseases.